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What is meant by the term "goitrogen" and what is the connection between goitrogens, food, and health?

"Goitrogen" is a medical term that is used to describe any substance that interferes with function of the thyroid gland. The word itself comes from "goiter," which means enlargement of the thyroid. If its ability to produce thyroid hormones becomes impaired, the thyroid gland can grow in size in an effort to keep up with the body's need for thyroid hormones.

Drugs and Chemical Toxins

It's important to remember that any substance that interferes with thyroid hormone production can be referred to as a "goitrogen," since that substance would be helping to generate the condition known as goiter. The best-studied human goitrogens are drugs and chemical toxins. In some cases, goitrogenic drugs have been intentionally developed for the express purpose of interfering with thyroid hormone production. These goitrogenic drugs—more commonly known as antithyroid drugs—are used to treat hyperthyroid problems, including Grave's disease. Other drugs—while not intended to interfere with thyroid function—can nevertheless have goitrogenic side effects. Iodine-containing prescription drugs, sulfonamides, and salicylamides are examples of medications that can have goitrogenic side effects.

In the chemical toxin category, perchlorate (a naturally occurring chemical, but also a man-made contaminant stemming from production of nitrate fertilizer with certain types of ore serving as the nitrogen source) and tobacco smoke (which contains hydrogen cyanide that can be converted into thiocyanate) are well-researched examples of chemical toxins that are considered goitrogenic because they can interfere with thyroid function. As you can see from these examples, the term "goitrogen" did not evolve in relationship with food but in a much broader medical context involving thyroid gland function and a wide range of factors that can disrupt it.

Glucosinolates in Food

Most of the in-depth research available to us about food components and thyroid function comes from animal studies. In these studies, the focus has been on cruciferous vegetables. These vegetables—all members of the Brassica family of plants—include broccoli, Brussels sprouts, cabbage, cauliflower, and mustard greens. Also included in this plant family is rape—the plant from which we not only get rapeseed but also rapeseed oil (which is the natural scientific name for canola oil).

Animal studies on mustard meal and rapeseed meal (common components in animal feed) are among our best sources of information about intake of cruciferous plants and thyroid function. These studies have focused on the total amount of glucosinolates present in the mustard seed and rapeseed meals. Glucosinolates are sulfur-containing phytonutrients originally synthesized in plants from sugars and amino acids. While not exclusively found in cruciferous vegetables, glucosinolates are especially concentrated in this food family. Over 125 different glucosinolates have been identified in cruciferous vegetables, and studies on these glucosinolates have shown them to have anti-cancer properties. (Commonly studied glucosinolates include glucophanin, glucobrassicin, sinigrin, gluconasturiian, and glucotropaeolin.) These anti-cancer properties do not come directly from the glucosinolates, however. These properties stem from conversion products of glucosinolates called thiocyanates. With the help of the enzyme myrosinase, each unique glucosinolate can be converted into a unique isothiocyanate. Glucophanin, for example, gets converted into sulforaphane. Glucobrassicin gets converted into indole-3-carbinol. All types of cruciferous vegetables contain many different glucosinolates. Brussels sprouts, for example, contain significant amounts of all glucosinolates listed above.

These same cancer-preventive isothiocyanates that can be formed from glucosinolates have been shown to potentially compromise thyroid function in very concentrated, high-dose amounts. But it is important to understand what counts as concentrated and high-dose within this context. We've seen studies on pigs, for example, in which unwanted thyroid effects did not arise so long as the pigs did not consume more than 4 ounces of rapeseed or mustard seed meal per kilogram of body weight per day. With 70 kilograms equating to 154 pounds, the equivalent amount of mustard or rapeseed meal intake for a person weighing this amount would be 280 ounces, or about 17 pounds. Obviously, this amount is far greater than any person would consume within a day's time.

In terms of concentration, animal studies have generally shown an absence of unwanted thyroid effects when glucosinolate concentrations fall below 4 milligrams per gram of mustard seed or rapeseed meal consumed. We have yet to see a study on fresh cruciferous vegetables in which the total glucosinolate content rises above 3 milligrams per gram. In fact, the total glucosinolate concentration in most fresh cruciferous vegetables falls between 0.6 and 1.0 milligrams per gram.

Another way of looking at this same information is to consider the amount of total glucosinolates in 1/2 cup of fresh cruciferous vegetables. All of the study results that we have seen in this area show an absolute minimum of 15 milligrams of total glucosinolates per half cup, and an absolute maximum of 260 milligrams. In practice, however, we have seldom seen 1/2-cup servings of fresh cruciferous vegetables averaging more than 100 milligrams of total glucosinolates. This amount is several hundred times smaller than the amount of total glucosinolates in animal feed that have been shown to interfere with thyroid function.

Other Goiter-Related Issues

Separate and apart from these glucosinolate-related studies on cruciferous vegetable intake and thyroid function, it's important to note that the number one cause of goiter worldwide is deficiency of the mineral iodine. Iodine is by far the most important mineral for understanding thyroid function, since it is not only a key component of all thyroid hormones but also serves as a regulator of thyroid function. Avoiding iodine deficiency is a key goal in prevention of goiter. One encouraging finding in this area has been the recognition that thyroid problems related to iodine deficiency can often be reversed through the resupplying of dietary iodine. In fact, one review study has suggested that unless 75% of iodine uptake by the thyroid has been lost over a period of several months, the disruption of thyroid hormone production can usually be reversed with restoration of adequate iodine. Our nutrient profile for iodine provides in-depth information about this important mineral.

Selenium deficiency is another dietary factor that has been linked with increased risk of goiter. Once again, our nutrient section contains a selenium profile with more in-depth information.

One final very interesting note: routine culinary use of the spice turmeric has been associated with decreased risk of goiter in some studies.

Impact of Cooking on Isothiocyanates

Although research studies are limited in this area, cooking does appear to inactivate a varying percentage of isothiocyanates in cruciferous vegetables. This amount appears to generally range from 0 to 33%. However, given the desirability of isothiocyanates from a cancer-preventing perspective, plus the unlikelihood of unwanted thyroid impacts from consumption of fresh cruciferous vegetables in everyday serving sizes, the cooking of cruciferous vegetables for the sole and exclusive purpose of lowering isothiocyanate content does not seem backed by sound research.

Isoflavones and the Thyroid

In addition to cruciferous vegetables, another food that is sometimes referred to as being "goitrogenic" is soybean. Just as research on glucosinolates helped to spark interest in cruciferous vegetables as potential goitrogenic foods, research on isoflavones helped to sparked interest in soybeans for this same reason. Like isothiocyanates, isoflavones are phytonutrients, and in this case, they are members of the flavonoid family as well. A large number of mixed studies exist with respect to the potential health benefits of isoflavone intake from soybeans and soy foods (like tofu or tempeh). Bone health, cardiovascular health, and cancer prevention are among the areas that have been closely studied—with a variety of mixed results.

The potential of isoflavone intake to negatively impact thyroid function has been investigated by researchers for two reasons. Both reasons involve biochemical events that take place at a cellular level. First, isoflavones have been shown to interfere with activity of an enzyme called thyroid peroxidase (TPO). TPO is an enzyme that helps attach iodine to an amino acid called tyrosine. This iodine-tyrosine combination forms the basis for production of thyroid hormones. How isoflavones are able to interfere with TPO activity is not fully understood.

A second set of cellular level events involves uptake of iodine into thyroid cells by a protein referred to as the sodium-iodide symporter (and abbreviated as "NIS," where the "N" comes from "Na," which is the scientific abbreviation for the element sodium). Like TPO activity, uptake of iodine into the thyroid cells by NIS can be interfered with by isoflavones. Once again, it is not completely clear how isoflavones are able to interfere with NIS activity.

In contract with these biochemical research studies that examine events at a cellular level are studies on actual intake of soy foods by humans. These studies—which include analysis of the isoflavones genistein, daidzein, malonylgenistin, and malonyldaidzin—show a limited impact of soy food intake on thyroid function, even when soy isoflavones are consumed in supplement form at levels higher than expected from food. For example, one small-scale study looked at the impact of 141 milligrams of dietary isoflavones from soy protein isolate each day over the course of one week and found no impact on thyroid measurements. Since soybeans contain approximately 3.5 milligrams of isoflavones per gram of protein, and since one cup of cooked soybeans contain about 29 grams of protein, we're talking about intake of approximately 100 milligrams of isoflavones from 1 cup of cooked soybeans, or an amount about 40% less than the supplemented amount that was found to have no impact on thyroid function. Additional studies have found no interference with thyroid function following supplementation of human diets with isolated soy protein, and at least one study has linked soy intake to thyroid support in postmenopausal women. Based on our review of the research, we cannot find a solid research basis for reducing soy food intake in order to decrease risk of thyroid problems. In this context, we would also add that we are more confident about the thyroid-related safety of natural soy foods—like cooked soybeans, fermented tofu or fermented tempeh—than the safety of highly processed soy components like isolated soy protein.

WHFoods Recommendations

In the absence of a solid research basis that demonstrates interference with thyroid function following routine intake of cruciferous vegetables or soy foods in everyday serving sizes, we believe that most everyone can enjoy the delicious taste and amazing nutritional and health benefits of these foods without having to be concerned with unwanted thyroid consequences.

References

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  • de Souza dos Santos MC, Goncalves CFL, Vaisman M et al. Impact of flavonoids on thyroid function. Food and Chemical Toxicology, Volume 49, Issue 10, October 2011, Pages 2495-2502.
  • Dong YH and Fu DG. Autoimmune thyroid disease: mechanism, genetics and current knowledge. Eur Rev Med Pharmacol Sci. 2014;18(23):3611-8.
  • Frisch T, Motawia MS, Olsen CE, et al. Diversified glucosinolate metabolism: biosynthesis of hydrogen cyanide and of the hydroxynitrile glucoside alliarinoside in relation to sinigrin metabolism in Alliaria petiolata. Front Plant Sci. 2015 Oct 31;6:926.
  • Hampl R, Ostatnikova D, Celec P et al. Short-term effect of soy consumption on thyroid hormone levels and correlation with phytoestrogen level in healthy subjects. Endocr Regul. 2008 Jun;42(2-3):53-61.
  • Leach PT and Gould TJ. Thyroid hormone signaling: Contribution to neural function, cognition, and relationship to nicotine. Neurosci Biobehav Rev. 2015 Oct;57:252-63.
  • Messina M and Redmond G. Effects of soy protein and soybean isoflavones on thyroid function in healthy adults and hypothyroid patients: a review of the relevant literature. Thyroid. 2006 Mar;16(3):249-58.
  • Sawicka-Gutaj N, Gutaj P, Sowinski J et al. Influence of cigarette smoking on thyroid gland--an update. Endokrynol Pol. 2014;65(1):54-62. doi: 10.5603/EP.2014.0008.
  • Silverstein MG, Kaplan JR, Appt SE, et al. Effect of soy isoflavones on thyroid hormones in intact and ovariectomized cynomolgus monkeys (Macaca fascicularis). Menopause. 2014 Oct;21(10):1136-42.
  • Teas J, Braverman LE, Kurzer MS, et al. Seaweed and soy: companion foods in Asian cuisine and their effects on thyroid function in American women. J Med Food. 2007 Mar;10(1):90-100.
  • Vanderpas J. Nutritional epidemiology and thyroid hormone metabolism. Annu Rev Nutr. 2006;26:293-322.
  • Wiersinga WM. Clinical Relevance of Environmental Factors in the Pathogenesis of Autoimmune Thyroid Disease. Endocrinol Metab (Seoul). 2016 May 13. [Epub ahead of print].
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